YOU ARE REQUIRED TO READ THE COPYRIGHT NOTICE AT THIS LINK BEFORE YOU READ THE FOLLOWING WORK, THAT IS AVAILABLE SOLELY FOR PRIVATE STUDY, SCHOLARSHIP OR RESEARCH PURSUANT TO 17 U.S.C. SECTION 107 AND 108. IN THE EVENT THAT THE LIBRARY DETERMINES THAT UNLAWFUL COPYING OF THIS WORK HAS OCCURRED, THE LIBRARY HAS THE RIGHT TO BLOCK THE I.P. ADDRESS AT WHICH THE UNLAWFUL COPYING APPEARED TO HAVE OCCURRED. THANK YOU FOR RESPECTING THE RIGHTS OF COPYRIGHT OWNERS.

A doctor draws blood from one of the Tuskegee test subjects.

The Tuskegee Syphilis Experiment (/tʌsˈkiːɡiː/)[1] was an infamous clinical study conducted between 1932 and 1972 by the U.S. Public Health Service to study the natural progression of untreated syphilis in rural African-American men in Alabama. They were told that they were receiving free health care from the U.S. government.[1]

The Public Health Service started working on this study in 1932 during the Great Depression, in collaboration with Tuskegee University, a historically black college in Alabama. Investigators enrolled in the study a total of 600 impoverished, African American sharecroppers from Macon County, Alabama. Of these men, 399 had previously contracted syphilis before the study began, and 201[2] did not have the disease. The men were given free medical care, meals, and free burial insurance for participating in the study. After funding for treatment was lost, the study was continued without informing the men they would never be treated. None of the men infected were ever told that they had the disease, and none were treated with penicillin even after the antibiotic became proven for the treatment of syphilis. According to the Centers for Disease Control, the men were told they were being treated for "bad blood", a local term for various illnesses that include syphilis, anemia, and fatigue.

The 40-year study was controversial for reasons related to ethical standards because researchers knowingly failed to treat patients appropriately after the 1940s validation of penicillin as an effective cure for the disease they were studying. Revelation in 1972 of study failures by a whistleblower led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies require informed consent [3] communication of diagnosis, and accurate reporting of test results.[4]

By 1947, penicillin had become the standard treatment for syphilis. Choices available to the doctors involved in the study might have included treating all syphilitic subjects and closing the study, or splitting off a control group for testing with penicillin. Instead, the Tuskegee scientists continued the study without treating any participants; they withheld penicillin and information about it from the patients. In addition, scientists prevented participants from accessing syphilis treatment programs available to other residents in the area.[5] The study continued, under numerous US Public Health Service supervisors, until 1972, when a leak to the press resulted in its termination on November 16 of that year.[6] The victims of the study, all African American, included numerous men who died of syphilis, 40 wives who contracted the disease, and 19 children born with congenital syphilis.[7]

The Tuskegee Syphilis Study, cited as "arguably the most infamous biomedical research study in U.S. history",[8] led to the 1979 Belmont Report and the establishment of the Office for Human Research Protections (OHRP).[9] It also led to federal laws and regulations requiring Institutional Review Boards for the protection of human subjects in studies involving them. The Office for Human Research Protections (OHRP) manages this responsibility within the US Department of Health and Human Services (HHS).[10]

History

Study clinicians

For the most part, doctors and civil servants simply did their jobs. Some merely followed orders, others worked for the glory of science.— John R. Heller Jr., Director of the Public Health Service's Division of Venereal Diseases[11]

Taliaferro Clark

Oliver Wenger

The venereal disease section of the U.S. Public Health Service (PHS) formed a study group in 1932 at its national headquarters. Taliaferro Clark was credited with founding it. His initial goal was to follow untreated syphilis in a group of black men for 6 to 9 months, and then follow up with a treatment phase. When he understood the intention of other study members to use deceptive practices, Clark disagreed with the plan to conduct an extended study. He retired the year after the study began.

Representing the PHS, Clark had solicited the participation of the Tuskegee Institute (a well-known historically black college in Alabama, now known as Tuskegee University) and of the Arkansas regional Public Health Service office.Eugene Heriot Dibble, Jr., an African-American doctor, was head of the John Andrew Hospital at the Tuskegee Institute. (From 1936-1946, he served as director of the Tuskegee Veterans Administration Medical Center, established in 1923 in the city by the federal government on land donated by the Institute.)

Oliver C. Wenger was the director of the regional PHS Venereal Disease Clinic in Hot Springs, Arkansas. He and his staff took the lead in developing study procedures. Wenger and his staff played a critical role in developing early study protocols. Wenger continued to advise and assist the Tuskegee Study when it was adapted as a long-term, no-treatment observational study after funding for treatment was lost.[12]

Raymond A. Vonderlehr was appointed on-site director of the research program and developed the policies that shaped the long-term follow-up section of the project. His method of gaining the "consent" of the subjects for spinal taps (to look for signs of neurosyphilis) was by portraying this diagnostic test as a "special free treatment". Participants were not told their diagnosis. Vonderlehr retired as head of the venereal disease section in 1943, shortly after the antibiotic penicillin had first been shown to be a cure for syphilis.

Several African American health workers and educators associated with Tuskegee Institute helped the PHS to carry out its experimentation and played a critical role in the progress of the study. The extent to which they knew about the full scope of the study is not clear in all cases. Dr. Robert Russa Moton, then president of Tuskegee Institute, and Dr. Eugene Dibble, head of the Institute's John Andrews Hospital, both lent their endorsement and institutional resources to the government study. Registered Nurse Eunice Rivers, who had trained at Tuskegee Institute and worked at its affiliated John Andrew Hospital, was recruited at the start of the study to be the main contact with the participants in the study.

Vonderlehr advocated Nurse Rivers' participation, as the direct link to the regional African-American community. During the Great Depression of the 1930s, the Tuskegee Study recruited poor lower-class African Americans, who often could not afford health care, by offering them the chance to join "Miss Rivers' Lodge". Patients were told they would receive free physical examinations at Tuskegee University, free rides to and from the clinic, hot meals on examination days, and free treatment for minor ailments.

Based on the available health care resources, Nurse Rivers believed that the benefits of the study to the men outweighed the risks. As the study became long term, Nurse Rivers became the chief person with continuity. Unlike the national, regional and on-site PHS administrators, doctors, and researchers, some of whom were political appointees with short tenure and others who changed jobs, Rivers continued at Tuskegee University. She was the only study staff person to work with participants for the full 40 years. By the 1950s, Nurse Rivers had become pivotal to the study: her personal knowledge of the subjects enabled maintenance of long-term follow up.

Historians found evidence that most of the African-American staff who assisted the Tuskegee Experiments believed that they were part of a medical experiment that was in the best interests overall of poor Black residents of Tuskegee.

In 1943 Congress passed the Henderson Act, a public health law requiring testing and treatment for venereal disease. By the late 1940s, doctors, hospitals and public health centers throughout the country routinely treated diagnosed syphilis with penicillin, but the Tuskegee experiment continued to avoid treating the men who had the disease.

In the period following World War II, the revelation of the Holocaust and related Nazi medical abuses brought about changes in international law. Western allies formulated the Nuremberg Code to protect the rights of research subjects. In 1964 the World Health Organization's Declaration of Helsinki specified that experiments involving human beings needed the “informed consent” of participants. But no one appeared to have reevaluated the protocols of the Tuskegee Study according to the new standards and in light of treatment available for the otherwise usually fatal disease.

In July 25, 1972 word of the Tuskegee Study was reported by Jean Heller of the Associated Press; the next day the New York Times carried it on its front page, and the story captured national attention. Peter Buxtun, a whistleblower who was a former PHS interviewer for venereal disease, had leaked information after failing to get a response to his protests about the study within the department. He gave information to the Washington Star and the New York Times. John R. Heller Jr. of PHS, who in later years of the study led the national division, still defended the ethics of the study, stating: "The longer the study, the better the ultimate information we would derive."[13] Author James Jones editorialized about Heller, suggesting that his opinion was: "The men's status did not warrant ethical debate. They were subjects, not patients; clinical material, not sick people."[14]

Raymond A. Vonderlehr (medical doctor)

Eugene Dibble (medical doctor)

Eunice Rivers (nurse)

Study details

Subject blood draw, c. 1953

A Norwegian study in 1928 had reported on the pathologic manifestations of untreated syphilis in several hundred white males. This study is known as a retrospective study, since investigators pieced together information from the histories of patients who had already contracted syphilis but remained untreated for some time.

Subjects talking with study coordinator, Nurse Eunice Rivers, c.1970

The Tuskegee study group decided to build on the Oslo work and perform a prospective study to complement it. In the earlier phases of the study, this was not inherently unethical since there was nothing the investigators could do therapeutically at the time. Researchers could study the natural progression of the disease as long as they did not harm their subjects. They reasoned that the knowledge gained would benefit humankind; however, it was determined afterward that the doctors did harm their subjects by depriving them of appropriate treatment once it had been discovered. The study was characterized as "the longest non-therapeutic experiment on human beings in medical history."[5]

The US Public Health Study of Syphilis at Tuskegee began as a 6-month descriptive epidemiological study of the range of pathology associated with syphilis in the Macon County population. At that time, it was believed that the effects of syphilis depended on the race of those affected. For African Americans, physicians believed that their cardiovascular system was more affected than the central nervous system.[15] Initially, subjects were studied for six to eight months and then treated with contemporary methods, including Salvarsan, mercurial ointments, and bismuth. These methods were, at best, mildly effective. The disadvantage that these treatments were all highly toxic was balanced by the fact that no other methods were known. The Tuskegee Institute participated in the study, as its representatives understood the intent was to benefit public health in the local poor population.[16] The Tuskegee University-affiliated hospital effectively loaned the PHS its medical facilities, and other predominantly black institutions and local black doctors participated as well.

The Rosenwald Fund, a major Chicago-based philanthropy devoted to black education and community development in the South, provided financial support to pay for the eventual treatment of the patients. They had previously collaborated with Public Health Services in a study of syphilis prevalence in over 2,000 black workers in Mississippi's Delta Pine and Land Company in 1928, and helped provide treatment for 25% of the workers who had tested positive for the disease.[17] Study researchers initially recruited 399 syphilitic Black men, and 201 healthy Black men as controls.

Table from U.S. Public Health Service summarising participants in the study

Continuing effects of the Stock Market Crash of 1929 and the beginning of the Great Depression led the Rosenwald Fund to withdraw its offer of funding. Study directors issued a final report as they thought this might mean the end of the study once funding to buy medication for the treatment phase of the study was withdrawn.

Medical ethics considerations were limited from the start and rapidly deteriorated. To ensure that the men would show up for the possibly dangerous, painful, diagnostic, and non-therapeutic spinal taps, the doctors sent the 400 patients a misleading letter titled "Last Chance for Special Free Treatment". The study also required all participants to undergo an autopsy after death in order to receive funeral benefits. After penicillin was discovered as a cure, researchers continued to deny such treatment to many study participants. Many patients were lied to and given placebo treatments so that researchers could observe the full, long-term progression of the fatal disease.[16]

Taking a blood sample as part of the Tuskegee Syphilis Study

The Tuskegee Study published its first clinical data in 1934 and issued its first major report in 1936. This was prior to the discovery of penicillin as a safe and effective treatment for syphilis. The study was not secret since reports and data sets were published to the medical community throughout its duration.

During World War II, 250 of the subject men registered for the draft. These men were consequently diagnosed as having syphilis at military induction centers and ordered to obtain treatment for syphilis before they could be taken into the armed services.[18] PHS researchers attempted to prevent these men from getting treatment, thus depriving them of chances for a cure. A PHS representative was quoted at the time saying: "So far, we are keeping the known positive patients from getting treatment."[18] Despite this, 96% of the 90 original test subjects reexamined in 1963 had received either arsenical or penicillin treatments from another health provider.[19]

By 1947 penicillin had become standard therapy for syphilis. The US government sponsored several public health programs to form "rapid treatment centers" to eradicate the disease. When campaigns to eradicate venereal disease came to Macon County, study researchers prevented their patients from participating.[18]

By the end of the study in 1972, only 74 of the test subjects were alive. Of the original 399 men, 28 had died of syphilis, 100 were dead of related complications, 40 of their wives had been infected, and 19 of their children were born with congenital syphilis. The Tuskegee University Legacy Museum has on display a check issued by the United States government on behalf of Dan Carlis to Lloyd Clements, Jr., a descendant of one of the Tuskegee Syphilis Study participants.[20] Lloyd Clements, Jr.'s great-grandfather Dan Carlis and two of his uncles, Ludie Clements and Sylvester Carlis, were in the study.

The first dissent against the Tuskegee study was Irwin Schatz, a young Chicago doctor only four years out of medical school. In 1965, Schatz read an article about the study in a medical journal, and wrote a letter directly to the study's authors confronting them with a declaration of brazen unethical practice.[21] His letter, read by Dr. Anne R. Yobs (one of the study's authors), was immediately ignored and filed away with a brief memo that no reply would be sent.[22]

In 1966 Peter Buxtun, a PHS venereal-disease investigator in San Francisco, sent a letter to the national director of the Division of Venereal Diseases to express his concerns about the ethics and morality of the extended Tuskegee Study. The Center for Disease Control (CDC), which by then controlled the study, reaffirmed the need to continue the study until completion; i.e., until all subjects had died and been autopsied. To bolster its position, the CDC received unequivocal support for the continuation of the study, both from local chapters of the National Medical Association (representing African-American physicians) and the American Medical Association (AMA).

In 1968 William Carter Jenkins, an African-American statistician in the PHS, part of the Department of Health, Education, and Welfare (HEW), founded and edited The Drum, a newsletter devoted to ending racial discrimination in HEW. The cabinet-level department included the CDC. In The Drum, Jenkins called for an end to the Tuskegee Study. He did not succeed; it is not clear who read his work.[23]

Buxtun finally went to the press in the early 1970s. The story broke first in the Washington Star on July 25, 1972. It became front-page news in the New York Times the following day. Senator Edward Kennedy called Congressional hearings, at which Buxtun and HEW officials testified. As a result of public outcry, the CDC and PHS appointed an ad hoc advisory panel to review the study. It determined the study was medically unjustified and ordered its termination.

As part of the settlement of a class action lawsuit subsequently filed by the NAACP on behalf of study participants and their descendants, the U.S. government paid $9 million (unadjusted for inflation) and agreed to provide free medical treatment to surviving participants and to surviving family members infected as a consequence of the study.

A collection of materials compiled to investigate the study is held at the National Library of Medicine in Bethesda, Maryland.[24]

Aftermath

In 1974 Congress passed the National Research Act and created a commission to study and write regulations governing studies involving human participants. Within the US Department of Health and Human Services, the Office of Human Research Protections (OHRP) was established to oversee clinical trials. Now studies require informed consent [3] communication of diagnosis, and accurate reporting of test results.[4] Institutional review boards (IRBs), including laypeople, are established in scientific research groups and hospitals to review study protocols and protect patient interests, to ensure that participants are fully informed.

In 1994, a multi-disciplinary symposium was held on the Tuskegee study: Doing Bad in the Name of Good?: The Tuskegee Syphilis Study and Its Legacy at the University of Virginia. Following that, interested parties formed the Tuskegee Syphilis Study Legacy Committee to develop ideas that had arisen at the symposium. It issued its final report in May 1996.[25] The Committee had two related goals: (1) President Bill Clinton should publicly apologize for past government wrongdoing related to the study and (2) the Committee and relevant federal agencies should develop a strategy to redress the damages.[26]

A year later on May 16, 1997, President Bill Clinton formally apologized and held a ceremony at the White House for surviving Tuskegee study participants. He said:

"What was done cannot be undone. But we can end the silence. We can stop turning our heads away. We can look at you in the eye and finally say on behalf of the American people, what the United States government did was shameful, and I am sorry ... To our African American citizens, I am sorry that your federal government orchestrated a study so clearly racist."[27]

Five of the eight study survivors attended the White House ceremony.

The presidential apology led to progress in addressing the second goal of the Legacy Committee. The federal government contributed to establishing the National Center for Bioethics in Research and Health Care at Tuskegee, which officially opened in 1999 to explore issues that underlie research and medical care of African Americans and other under-served people.[28]

In 2009 the Legacy Museum opened in the Bioethics Center, to honor the hundreds of participants of the Tuskegee Study of Untreated Syphilis in the Negro Male. [28][29]

The revelations of mistreatment under the Tuskegee Syphilis Study are believed to have significantly damaged the trust of the black community toward public health efforts in the United States.[30] Observers believe that the abuses of the study may have contributed to the reluctance of many poor black people to seek routine preventive care.[31] But, studies in the early 21st century, such as the Tuskegee Legacy Project Questionnaire, have challenged the degree to which knowledge of the Tuskegee experiments have kept black Americans from participating in medical research.[32] This study shows that, even though black Americans are four times more likely to know about the Syphilis trials than are whites, they are two to three times more willing to participate in biomedical studies.[33] Other studies concluded that the Tuskegee Syphilis trial has played a minor role in the decisions of black Americans to decline participation as research subjects.[34] There are few studies that have investigated the willingness of black Americans to participate in medical studies, however, and researchers have not drawn consistent conclusions related to the willingness and participation in studies by racial minorities. Some of the factors that continue to limit the credibility of these few studies is how awareness differs significantly across studies. For instance, it appears that the rates of awareness differ as a function of method of assessment, study participants who reported awareness of the Tuskegee Syphilis Trials are often misinformed about the results and issues, and awareness of the study is not reliably associated with unwillingness to participate in scientific research.[35][36][37][38][39] Distrust of the government because of the study contributed during the 1980s to persistent rumors in the black community that the government was responsible for the HIV/AIDS crisis by having deliberately introduced the virus to the black community as some kind of experiment.[40] In February 1992 on ABC's Prime Time Live, journalist Jay Schadler interviewed Dr. Sidney Olansky, Public Health Services director of the study from 1950 to 1957. When asked about the lies that were told to the study subjects, Olansky said, "The fact that they were illiterate was helpful, too, because they couldn't read the newspapers. If they were not, as things moved on they might have been reading newspapers and seen what was going on." [17]

Ethical implications

Depression-era U.S. poster advocating early syphilis treatment. Although treatments were available, participants in the study did not receive them.

Tuskegee highlighted issues in race and science.[41] The aftershocks of this study, and other human experiments in the United States, led to the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the National Research Act. The latter requires the establishment of institutional review boards (IRBs) at institutions receiving federal support (such as grants, cooperative agreements, or contracts). (though foreign consent procedures can be substituted which offer similar protections; such substitutions must be submitted to the Federal Register unless statute or Executive Order require otherwise).

Writer James Jones says that physicians were fixated on African American sexuality and, believing that African Americans willingly had sexual relations with those who were infected (although none had been told his diagnosis) resulted in their believing that individuals were solely responsible for contracting the disease.[42] One researcher critiqued how the study was administered and its change in purpose. He said that it was "the economic exploitation of humans as a natural resource of a disease that could not be cultivated or animals in order to establish and sustain U.S. superiority in patented commercial biotechnology”.[43]

Some commentators say that the Tuskegee study was progressive for its inclusion of minorities in scientific research being funded by the federal government.[44]

Due to the lack of information, the participants were manipulated into continuing the study without full knowledge of their role or their choices.[45] Since the late 20th century, IRBs established in association with clinical studies require that all involved in study be willing and voluntary participants.[46][47]

Maron County Health DepartmentALABAMA STATE BOARD OF HEALTH AND U.S. PUBLIC HEALTH SERVICE COOPERATING WITH TUSKEGEE INSTITUTEDear Sir:Some time ago you were given a thorough examination and since that time we hope you have gotten a great deal of treatment for bad blood. You will now be given your last chance to get a second examination. This examination is a very special one and after it is finished you will be given a special treatment if it is believed you are in a condition to stand it.If you want this special examination and treatment you must meet the nurse at _____ on _____ at ______M. She will bring you to the Tuskegee Institute Hospital for this free treatment. We will be very busy when these examinations and treatments are being given, and will have lots of people to wait on. You will remember that you had to wait for some time when you had your last good examination, and we wish to let you know that because we expect to be so busy it may be necessary for you to remain in the hospital over one night. If this is necessary you will be furnished your meals and a bed, as well the examination and treatment without cost.REMEMBER THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT. BE SURE TO MEET THE NURSE.Macon County Health Department]

Document from Tuskegee Syphilis Study, requesting that after test subjects die, an autopsy be performed, and the results sent to the National Institutes of Health

[AUTOPSIESGeneral Information and Procedure: These autopsies are performed in connection with the Study of Untreated Syphilis in the Male Negro which is being conducted by the Public Health Service in cooperation with the Alabama State Board of Health, the Macon County Health Unit and the Tuskegee Institute. Doctor Murray Smith is in charge of this study and as a Special Expert of the U.S. Public Health Service is addressed in care of the County Health Department, Tuskegee, Alabama.Upon the death and post mortem examination of a patient included in this study, Tuskegee will send an autopsy report on the case to the Division of Venereal Diseases in Washington. Three copies of the autopsy will be prepared and forwarded as follows: one copy to [Deleted: Senior Surgeon Ralph D. Lillie,] [Handwritten: Chief,] Division of Pathology, National Institute of Health; [Deleted: one copy to P.A. Surgeon Austin V. Deibert;] and one copy retained in the Autopsy File in the Division of Venereal Diseases.On specimens sent direction to the National Institute of Health from Tuskegee, an examination is done and copies of the report sent to the Division of Venereal Diseases in Washington, [Deleted: Three] [Handwritten: One] copies of this report will be prepared and forwarded [Handwritten: upon receipt of NIH findings make one copy and send to Dr. J.J. Peters, Veterans, Administration Hospital, Tuskegee, Ala.] as follows: [Deleted: one copy to P.A. Surgeon Austin V. Deibert; one copy to Special Consultant C.A. Walwyn, U.S. Public Health Service, c/o John A. Andrew Memorial Hospital,] Tuskegee, Alabama; and one copy retained in the Autopsy File in the Division of Venereal Diseases.All data pertaining to one case will be clipped together and properly recorded on Record of Autopsies sheet.]

Draft report of study results up to 1949, page 1

[Alabama Untreated Syphilis Study[Handwritten: Progression of Abnormalities over 16 yrs"?]This paper is the fourth of a series of studies of untreated acquired syphilis in the male Negro in Macon County, Alabama. Previous papers have death with [handwritten: (1)] the [Deleted: extent of morbidity] [Handwritten: various abnormalities found] in untreated syphilitics [Deleted: in comparison with] [Handwritten: and] nonsyphilitic controls, [Handwritten: at the time of the initial examination,] the life expectancy of the respective groups [Handwritten: after 10 years observation, (2)] the natural history of syphilis, uninfluenced by treatment, with special attention to [Deleted: its] [Handwritten: the] effect [Handwritten: of the disease] on the cardiovascular system [Handwritten: after 5 yrs. observation and] The present study is [Deleted: an] [Handwritten: a report made after 16 years observation and is an] attempt to estimate the [Deleted: progressive disability] [Handwritten: increment of abnormalities among untreated syphilitics and nonsyphilitic controls [Deleted: during 16 years of observation.] [Handwritten: occurring during that 16 yr. period. How are these different? HOK]The original study population selected during [Handwritten: (] the winter [Deleted: seasons] [Handwritten: months] of 1931-32 and 1932-33 consisted of 410 syphilitics and 201 [Handwritten: controls presumably] nonsyphilitic [Deleted: controls,] all of [Deleted: which] [Handwritten: whom] were 25 years of age or [Deleted: more.] [Handwritten: older.] [Deleted: The individuals were carefully selected.] The presence or absence of syphilitic infection was based on personal history, physical examination, and serologic tests on the blood. [Deleted: Before the present far-reaching aims of the study were actually set up, 179] Of the syphilitic group [Handwritten: 179] were given some treatment for their infection during the ... [ Handwritten: What was the study Pop selected for??? HAK. To be referred to a specific page in first paper. KAZ.]

Draft report of study results up to 1949, page 2

[period of this first examination. Most of these individuals were among the younger age groups, and were given amounts of treatment varying from 1 to 15 shots of neoarsephenamine. [Handwritten: These have been dropped from consideration in the present paper.] A second complete physical examination was made of the majority in 1938-30. [Deleted: However, no strenuous effort was made to locate those who had received treatment, and consequently a large number of them lapsed from observation.] Since 1939, there has been an annual visit to Macon County by a physician for the purpose of obtaining specimens of blood for serologic examination. In the fall of 1948, a third physical examination was performed on the individuals who could be located at that time, [Deleted: again with the particular emphasis on those who had received some treatment.]An important phase of the study has been the performance of autopsies on the individuals who have died. Through 1948, [Deleted: 163] [Handwritten: 140] of the number included in the original population have died, and of these [Deleted: 111] [Handwritten: 98] have been autopsied. Of those [handwritten: on] whom [Deleted: have not been autopsied] [handwritten: the autopsies have not been performed,] proof of death has been established by death certificate or by information furnished by relatives or friends of the deceased. Because of the relatively non-migratory nature of the group, it is reasonably certain that there have been no other deaths than the [Deleted: 163] [Handwritten: 140] recorded. No analysis of autopsy data will be attempted in this report; a detailed account of this ...]

Table depicting number of subjects with syphilis and number of controlled non-syphlitic patients, and how many of the subjects have died during the experiments, 1969

MEMORANDUMDEPARTMENT OF HEALTH, EDUCATION, AND WELFAREOFFICE OF THE SECRETARYDATE: NOV. 16, 1972TO: DirectorCenter for Disease Control THROUGH: Administrator, HS __ 11/22FROM: Assistant Secretary for HealthSUBJECT: Termination of USPHS Study of Untreated Syphilis (the Tuskegee Study)As recommended by the Tuskegee Syphilis Study Ad Hoc Advisory Panel, I have decided that the "Tuskegee Study" as a study of untreated syphilis must be terminated. I will advise you of the necessary steps to be taken to assure that appropriate medical care be given to all remaining participants in the "Tuskegee Study" as a part of the close-out phase of the project.Merlin K. DuVal, M.D.

• U.S. Public Health Service Syphilis Study at Tuskegee, at the Center for Disease Control• Review of the TSS• Patient medical files held at National Archives and Records Administration Southeast Region, Morrow, GA• Tuskegee Syphilis Study article, Encyclopedia of Alabama• 'Nurse Eunice Rivers'• Bad Blood: The Tuskegee Syphilis Study. Claude Moore Health Sciences Library, University of Virginia• The Tuskegee Syphilis Study and Its Implications for the 21st Century

YOU ARE REQUIRED TO READ THE COPYRIGHT NOTICE AT THIS LINK BEFORE YOU READ THE FOLLOWING WORK, THAT IS AVAILABLE SOLELY FOR PRIVATE STUDY, SCHOLARSHIP OR RESEARCH PURSUANT TO 17 U.S.C. SECTION 107 AND 108. IN THE EVENT THAT THE LIBRARY DETERMINES THAT UNLAWFUL COPYING OF THIS WORK HAS OCCURRED, THE LIBRARY HAS THE RIGHT TO BLOCK THE I.P. ADDRESS AT WHICH THE UNLAWFUL COPYING APPEARED TO HAVE OCCURRED. THANK YOU FOR RESPECTING THE RIGHTS OF COPYRIGHT OWNERS.

From 1946 to 1948, American public health doctors deliberately infected nearly 700 Guatemalans — prison inmates, mental patients and soldiers — with venereal diseases in what was meant as an effort to test the effectiveness of penicillin.

American tax dollars, through the National Institutes of Health, even paid for syphilis-infected prostitutes to sleep with prisoners, since Guatemalan prisons allowed such visits. When the prostitutes did not succeed in infecting the men, some prisoners had the bacteria poured onto scrapes made on their penises, faces or arms, and in some cases it was injected by spinal puncture.

If the subjects contracted the disease, they were given antibiotics.

“However, whether everyone was then cured is not clear,” said Susan M. Reverby, the professor at Wellesley College who brought the experiments to light in a research paper that prompted American health officials to investigate.

The revelations were made public on Friday, when Secretary of State Hillary Rodham Clinton and Health and Human Services Secretary Kathleen Sebelius apologized to the government of Guatemala and the survivors and descendants of those infected. They called the experiments “clearly unethical.”

“Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health,” the secretaries said in a statement. “We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices.”

In a twist to the revelation, the public health doctor who led the experiment, John C. Cutler, would later have an important role in the Tuskegee study in which black American men with syphilis were deliberately left untreated for decades. Late in his own life, Dr. Cutler continued to defend the Tuskegee work.

His unpublished Guatemala work was unearthed recently in the archives of the University of Pittsburgh by Professor Reverby, a medical historian who has written two books about Tuskegee.

President Álvaro Colom of Guatemala, who first learned of the experiments on Thursday in a phone call from Mrs. Clinton, called them “hair-raising” and “crimes against humanity.” His government said it would cooperate with the American investigation and do its own.

The experiments are “a dark chapter in the history of medicine,” said Dr. Francis S. Collins, director of the National Institutes of Health. Modern rules for federally financed research “absolutely prohibit” infecting people without their informed consent, Dr. Collins said.

Professor Reverby presented her findings about the Guatemalan experiments at a conference in January, but nobody took notice, she said in a telephone interview Friday. In June, she sent a draft of an article she was preparing for the January 2011 issue of the Journal of Policy History to Dr. David J. Sencer, a former director of the Centers for Disease Control. He prodded the government to investigate.

In the 1940s, Professor Reverby said, the United States Public Health Service “was deeply interested in whether penicillin could be used to prevent, not just cure, early syphilis infection, whether better blood tests for the disease could be established, what dosages of penicillin actually cured infection, and to understand the process of re-infection after cures.”

It had difficulties growing syphilis in the laboratory, and its tests on rabbits and chimpanzees told it little about how penicillin worked in humans.

Susan M. Reverby, a Wellesley College professor, at home in Cambridge, Mass. Her work uncovered the Guatemala study. Credit Bryce Vickmark for The New York Times

In 1944, it injected prison “volunteers” at the Terre Haute Federal Penitentiary in Indiana with lab-grown gonorrhea, but found it hard to infect people that way.

In 1946, Dr. Cutler was asked to lead the Guatemala mission, which ended two years later, partly because of medical “gossip” about the work, Professor Reverby said, and partly because he was using so much penicillin, which was costly and in short supply.

Dr. Cutler would later join the study in Tuskegee, Ala., which had begun relatively innocuously in 1932 as an observation of how syphilis progressed in black male sharecroppers. In 1972, it was revealed that, even when early antibiotics were invented, doctors hid that fact from the men in order to keep studying them. Dr. Cutler, who died in 2003, defended the Tuskegee experiment in a 1993 documentary.

Deception was also used in Guatemala, Professor Reverby said. Dr. Thomas Parran, the former surgeon general who oversaw the start of Tuskegee, acknowledged that the Guatemala work could not be done domestically, and details were hidden from Guatemalan officials.

Professor Reverby said she found some of Dr. Cutler’s papers at the University of Pittsburgh, where he taught until 1985, while she was researching Dr. Parran.

“I’m sifting through them, and I find ‘Guatemala ... inoculation ...’ and I think ‘What the heck is this?’ And then it was ‘Oh my god, oh my god, oh my god.’ My partner was with me, and I told him, ‘You aren’t going to believe this.’ ”

Fernando de la Cerda, minister counselor at the Guatemalan Embassy in Washington, said that Mrs. Clinton apologized to President Colom in her Thursday phone call. “We thank the United States for its transparency in telling us the facts,” he said.

Asked about the possibility of reparations for survivors or descendants, Mr. de la Cerda said that was still unclear.

The public response on the Web sites of Guatemalan news outlets was furious. One commenter, Cesar Duran, on the site of Prensa Libre wrote: “APOLOGIES ... please ... this is what has come to light, but what is still hidden? They should pay an indemnity to the state of Guatemala, not just apologize.”

Dr. Mark Siegler, director of the Maclean Center for Clinical Medical Ethics at the University of Chicago’s medical school, said he was stunned. “This is shocking,” Dr. Siegler said. “This is much worse than Tuskegee — at least those men were infected by natural means.”

He added: “It’s ironic — no, it’s worse than that, it’s appalling — that, at the same time as the United States was prosecuting Nazi doctors for crimes against humanity, the U.S. government was supporting research that placed human subjects at enormous risk.”

The Nuremberg trials of Nazi doctors who experimented on concentration camp inmates and prisoners led to a code of ethics, though it had no force of law. In the 1964 Helsinki Declaration, the medical associations of many countries adopted a code.

The Tuskegee scandal and the hearings into it conducted by Senator Edward M. Kennedy became the basis for the 1981 American laws governing research on human subjects, Dr. Siegler said.

It was preceded by other domestic scandals. From 1963 to 1966, researchers at the Willowbrook State School on Staten Island infected retarded children with hepatitis to test gamma globulin against it. And in 1963, elderly patients at the Brooklyn Jewish Chronic Disease Hospital were injected with live cancer cells to see if they caused tumors.